17-82036754-C-G

Variant names:

• chr17-82036754-C-G
• NM_016286.4:c.315G>C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_016286.4(DCXR):​c.315G>C​(p.Glu105Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: DCXR NM_016286.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.06

Genes affected

DCXR (HGNC:18985): (dicarbonyl and L-xylulose reductase) The protein encoded by this gene acts as a homotetramer to catalyze diacetyl reductase and L-xylulose reductase reactions. The encoded protein may play a role in the uronate cycle of glucose metabolism and in the cellular osmoregulation in the proximal renal tubules. Defects in this gene are a cause of pentosuria. Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Aug 2010]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.049924016).
• BP6: Variant 17-82036754-C-G is Benign according to our data. Variant chr17-82036754-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2299970.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCXR	NM_016286.4	c.315G>C	p.Glu105Asp	missense_variant	Exon 4 of 8	ENST00000306869.7	NP_057370.1
DCXR	NM_001195218.1	c.309G>C	p.Glu103Asp	missense_variant	Exon 4 of 8		NP_001182147.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCXR	ENST00000306869.7	c.315G>C	p.Glu105Asp	missense_variant	Exon 4 of 8	1	NM_016286.4	ENSP00000303356.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jul 07, 2022

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	0.0010
DANN	Benign	0.48
DEOGEN2	Benign	0.032	.;T;T;T
Eigen	Benign	-2.6
Eigen_PC	Benign	-2.7
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.79	T;T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.050	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.41	.;N;.;.
PrimateAI	Benign	0.37	T
PROVEAN	Benign	1.1	.;N;.;.
REVEL	Benign	0.051
Sift	Benign	0.43	.;T;.;.
Sift4G	Benign	0.65	T;T;.;T
Polyphen		0.0	.;B;.;.
Vest4		0.14
MutPred		0.48		.;Gain of sheet (P = 0.0827);.;.;
MVP		0.50
MPC		0.32
ClinPred		0.030	T
GERP RS		-10
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.17
gMVP		0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-79994630;